A critical role for direct TLR2-MyD88 signaling in CD8 T-cell clonal expansion and memory formation following vaccinia viral infection.
Recent advances have suggested a crucial role of the innate immunity in shaping adaptive immune responses. How activation of innate immunity promotes adaptive T-cell responses to pathogens in vivo is not fully understood. It has been thought that Toll-like receptor (TLR)-mediated control of adaptive T-cell responses is mainly achieved by the engagement of TLRs on antigen-presenting cells to promote their maturation and function. In this study, we showed that direct TLR2-myeloid differentiating factor 88 (MyD88) signaling in CD8 T cells was also required for their efficient clonal expansion by promoting the survival of activated T cells on vaccinia viral infection in vivo. Effector CD8 T cells that lacked direct TLR2-MyD88 signaling did not survive the contraction phase to differentiate into long-lived memory cells. Furthermore, we observed that direct TLR2 ligation on CD8 T cells promoted CD8 T-cell proliferation and survival in vitro in a manner dependent on the phosphatidylinositol 3-kinase (PI3K)-Akt pathway activation and that activation of Akt controlled memory cell formation in vivo. These results identify a critical role for intrinsic TLR2-MyD88 signaling and PI3K-Akt pathway activation in CD8 T-cell clonal expansion and memory formation in vivo and could lead to the development of new vaccine approaches.
Quigley
Michael
M
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Martinez
Jennifer
J
Huang
Xiaopei
X
Yang
Yiping
Y
D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation; D002999:Clone Cells; D005434:Flow Cytometry; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*; D014615:Vaccinia / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt